Highly Stereodivergent Construction of a C 2 -Symmetric cis , cis - and trans , trans -2,6-Dioxabicyclo[3.3.0]octane Framework by Double Intramolecular Amide Enolate Alkylation: Total Synthesis of (+)-Laurenidificin and (+)-Aplysiallene.

The highly stereoselective construction of C 2 -symmetric cis , cis - and trans , trans -2,6-dioxabicyclo[3.3.0]octane (fused bis -tetrahydrofuran) skeletons 4a and 4b has been accomplished via a novel stereodivergent double intramolecular amide enolate alkylation of common cyclization substrate 5 through the judicious choice of "chelate" versus crown ether-promoted "nonchelate" control. Application of this methodology has provided access to substrate-controlled concise total syntheses of (+)-laurenidificin ( 3 ) and (+)-aplysiallene ( ent - 2 ), which possess cis / cis - and trans / trans -fused bis-tetrahydrofuran cores, respectively.